Mitogenic factors are a requirement for the proliferation, migration, differentiation, maintenance and survival of multicellular organisms. The fate of many individual cells, e.g., proliferation, migration, differentiation, or interaction with other cells, is typically governed by information received from other cells and/or the immediate environment. This information is often transmitted by secreted polypeptides, such as mitogenic factors.
Stem cells are undifferentiated cells capable of (a) proliferation, (b) self maintenance, (c) the production of a large number of differentiated functional progeny, (d) regeneration of tissue after injury and/or (e) flexibility in the use of these options. Stem cells are important and ideal targets for gene therapy where the inserted genes promote the health of the individual into whom the stem cells are transplanted. Moreover, stem cells may play important roles in transplantation of organs or tissues, for example liver regeneration and skin grafting.
For example, neural stem cells (NSCs) are undifferentiated cells that have the ability to self renew and differentiate into neuronal and glial phenotypes. A primary concern in stem cell research is determining optimal conditions for the expansion of NSCs in clinically relevant numbers while maintaining normal karyotype and consistent differentiation capacities. The concept of a stem cell cellular differentiation is shown in FIG. 1 (Shihabuddin et al., Mol Med Today Vol. 5, (1999)). Presently, the only method to achieve expansion of NSCs is either by genetic modification to establish an immortalized cell line or by stimulating the cells with exogenous mitogenic factors such as fibroblast growth factor (FGF) and epidermal growth factor (EGF). Nonetheless, the cost of using a mitogenic factor as a therapeutical agent is expensive.
Light therapy (LT), also known as photo-biomodulation or low power laser irradiation (LPLI), is a non-invasive treatment which evokes biological effects via the absorption of light. LPLI has been shown to increase neuronal survival and regeneration in the peripheral nervous system (Anders, et al., Surg. Med, 13:72-82 (1993), Snyder, et al., Surg. Med, 31:216-222 (2002)). Investigation has shown that LT, through the absorption of light by a cellular photoreceptor, rather than heating of the cell (Anders, et al., Surg Med. 13:72-82, (1993), and Mochizuki-Oda, et al., Neurosci. Lett. 323:207-210 (2002)), can increase or decrease ATP, DNA, RNA and protein synthesis, depending on the treatment parameters applied (Saperia, et al., Biochem. Biophys. Res. Commun. 138:1123-1128 (1986); Greco, et al., Biochem. Biophys. Res. Commun. 163:1428-1434 (1989); Lam, et al., Lasers Life Sci. 1:61-77 (1986); Funk, et al., J. Photochem. Photobiol. B:BBiol. 16:347-355 (1992); Mochizuki-Oda, et al., Supra (2002)).
LT, however, has not been used as a replacement for mitogenic factors to support cellular survivability, proliferation, differentiation and migration.